Enzyme potentiated desensitization (EPD)
Enzyme potentiated desensitization (EPD) is an alternative therapy aimed at preventing allergies through the injection of low doses of allergens combined with the enzyme beta-glucuronidase. Developed in the 1960s by physician Leonard McEwan in the UK, EPD is believed by proponents to "retrain" the immune system, potentially offering lasting relief from various allergies and even a range of other medical conditions, such as rheumatoid arthritis and attention deficit hyperactivity disorder. However, the scientific support for these claims is limited and often considered unreliable, primarily relying on non-rigorous studies. Only two randomized, double-blind, placebo-controlled trials have been conducted, yielding mixed results regarding EPD’s efficacy for allergies, with one study showing no significant difference between EPD and placebo groups.
Despite the lack of substantial evidence, EPD has not been approved by the U.S. Food and Drug Administration since the early 2000s, and attempts to reintroduce it under different names have been met with skepticism. While the therapy may be relatively safe, with few serious adverse reactions reported, the potential for allergic reactions and the actual effectiveness of EPD remain uncertain. It is essential for individuals considering this treatment to thoroughly research and consult healthcare professionals before pursuing EPD.
On this Page
Enzyme potentiated desensitization (EPD)
- DEFINITION: A therapy involving injection of substances to prevent allergies.
- PRINCIPAL PROPOSED USE: Allergic rhinitis
- OTHER PROPOSED USES: Hundreds of conditions
Overview
Enzyme potentiated desensitization (EPD) is an alternative form of “allergy shot” originally popularized in the United Kingdom in the 1960s by physician Leonard McEwan. EPD involves the injection of very low levels of an allergen combined with the naturally occurring enzyme beta-glucuronidase. EPD proponents claim that this method treats the source of allergy problems and produces permanent benefits by “retraining” the immune system. It is claimed that EPD can treat hundreds of medical conditions, including rheumatoid arthritis, epilepsy, bug bites, food allergies, attention deficit hyperactivity disorder, and much more. However, the evidence used to support these assertions falls considerably short of meaningful.
EPD proponents cite studies that show EPD offers cure rates approaching 85 percent for numerous illnesses. However, the evidence for this is scientifically unreliable. The cited research was of the type called an “open, uncontrolled” study. This means that researchers (or practitioners) administered EPD to people and then noted whether they saw benefit. Positive findings in this type of investigation may seem intuitively to mean something, but they are actually illusions. For most conditions, a high percentage of people given placebo will improve or appear to improve, and they often will do so dramatically.
The reasons for this fact are complicated and surprising. For researchers to actually show a treatment to be effective, they must compare it with placebo treatment. Furthermore, they must conduct the study in a double-blind fashion, meaning that neither the practitioners nor the participants know who is getting real treatment and who is getting placebo. Finally, such studies must be randomized, meaning that people are assigned to the treatment or the placebo group by random chance (such as by flipping a coin) rather than by choice. Only two such randomized, double-blind, placebo-controlled trials have been performed on EPD. One found benefit, and the other did not.
In the first double-blind, placebo-controlled study, 183 people with a history of consistent hay fever were treated with EPD or placebo and followed throughout the hay fever season. The EPD preparation contained beta-glucuronidase, 1,3-cyclohexanediol, protamine sulfate, and a mixed extract of allergens, including pollens, fungal spores, cat and dog dander, and dust mites. The fake treatment contained only saline. Neither the researchers administering the injections nor the study participants knew which was which. Both groups improved markedly. However, there was no difference in symptoms between the two groups, as measured by problem-free days, quality-of-life scores, or symptom severity scores.
A slightly smaller study did find benefits. In this double-blind study of 125 children, the use of a single dose of EPD reduced hay fever and asthma symptoms compared with placebo. The most that can be said about EPD is that equivocal evidence exists regarding its efficacy for allergies. Benefits for any other conditions remain entirely speculative.
A similar scientific inadequacy exists regarding claims made about how EPD works. One EPD website stated the following:
EPD stimulates the immune system to produce new T-suppressor cells . . . These take 3 to 4 weeks to mature before they can begin their task of disabling mis-coded T-Helper cells. Essentially, this is a re-training program so the body does not react to those substances contained in the shot. The mis-coded cells are a part of the chain that stimulates the production of histamine, the major trigger of allergic response.
While this claim may sound impressive, it succeeds only as advertising; as science, it strays much too far from established facts.
EPD has been banned by the US Food and Drug Administration since the early twenty-first century, and despite attempts to repackage and reintroduce EPD as a Low Dose Allergen (LDA) treatment, it remains a dubious healthcare practice. Studies in the 2020s, however, do suggest health benefits of beta-glucuronidase, just within different medical contexts.
Safety Issues
While EPD is not likely effective, the limited body of imperfect research on the method indicates it may be relatively safe. No serious adverse reactions have been associated with its use. However, not enough confirmatory research exists to support its safety. In theory, allergic reactions could occur in response to EPD injections, the amount of allergen used in EPD is so much lower than the amount used in a normal “allergy shot” that allergic reactions may not, in fact, occur. Finally, EPD proponents claim that there can be a temporary aggravation response that is part of the healing process; however, this has not been documented.
Bibliography
Abramson, Michael J., et al. “Injection Allergen Immunotherapy for Asthma.” Cochrane Database of Systematic Reviews, no. 8, 2010, doi.org/info:doi/10.1002/14651858.CD001186.pub2. Accessed 1 Dec. 2024.
Awolade, Paul, et al. "Therapeutic Significance of β-glucuronidase Activity and Its Inhibitors: A Review." European Journal of Medicinal Chemistry, vol. 187, 2020, pp. 111921, doi.org/10.1016/j.ejmech.2019.111921. Accessed 1 Dec. 2024.
Berkovitz, S., et al. “A Randomised, Double-Blind Pilot Study of Enzyme-Potentiated Desensitisation for Prophylaxis of Large Local Reactions to Mosquito Bites.” Journal of Allergy, 2012, p. 106069, doi.org/10.1155/2012/106069. Accessed 1 Dec. 2024.
Calderon, Moises A., et al. “Allergen Injection Immunotherapy for Seasonal Allergic Rhinitis.” Cochrane Database of Systematic Reviews, no. 1, 2009, doi.org/info:doi/10.1002/14651858.CD001936.pub2. Accessed 1 Dec. 2024.
Galli, E., et al. “A Double-Blind Randomized Placebo-Controlled Trial with Short-Term Beta-Glucuronidase Therapy in Children with Chronic Rhinoconjunctivitis and/or Asthma Due to Dust Mite Allergy.” Journal of Investigational Allergology & Clinical Immunology, vol. 16, no. 6, 2006, pp. 345–50, pubmed.ncbi.nlm.nih.gov/17153881. Accessed 1 Dec. 2024.
Lockey, Richard F., and Dennis K. Ledford. "Allergens and Allergen Immunotherapy: Subcutaneous, Sublingual, and Oral." Unproven and Epicutaneous and Other Investigational Forms of Immunotherapy. 6th ed., CRC Press/Taylor and Francis Group, 2020, pp. 485-91.
Radcliffe, Michael J., et al. “Enzyme Potentiated Desensitisation in Treatment of Seasonal Allergic Rhinitis: Double Blind Randomised Controlled Study.” BMJ: British Medical Journal, vol. 327, no. 7409, 2003, pp. 251–54, doi:10.1136/bmj.327.7409.251. Accessed 1 Dec. 2024.